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Modification of natural killer activity of lymphocytes infiltrating human lung cancers

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Summary

The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxic activity and to determine its modulation by biologic agents. Local immunity may be an important component in limiting local tumor growth. Therefore, as a model for studying immune function in the local compartment, we assessed NK activity of lymphocytes present at the site of human tumors and in peripheral blood (PBL). We extracted tumor infiltrating lymphocytes (TIL) and PBL from patients with pulmonary tumors and compared NK activity and response to the biological modifiers gamma interferon (IFN-γ), indomethacin (INDO), and interleukin 2 (IL-2). We also studied TIL and PBL LAK activity using the NK-resistant M14 target cells and determined the TIL response to IL-2, plus IFN-γ. Titration of K562 targets in a 51Cr release assay revealed that untreated TIL have low cytotoxicity (4.32%) compared to untreated PBL (34.3%, P=<0.001). This low level of TIL NK activity was not affected by IFN-γ, INDO, or IL-2 at 1 h. However, at 3 days of culture, IL-2 with or without exogenous IFN-γ significantly increased TIL NK ctotoxicity (20.5%, P=0.02 without IFN-γ and 32.52 lytic units (LU), P=<0.02 with IFN-γ). Untreated TIL and PBL both had low cytotoxicity against M14 targets (1.08 LU and 1.26 LU), respectively. After 3 days culture with IL-2 plus IFN-γ, both TIL and PBL LAK cytotoxicity were increased (14.34 LU and 40.63 LU). We conclude that local NK and LAK activity is intrinsically low. However, this activity can be modulated by biologic agents, thus giving hope for the development of local antitumor effectors capable of in vivo tumor control.

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References

  1. Amagai T, Masakazu K, Imanishi J, Tsunataro K (1983) Augumentation of natural killer activity of human peripheral blood lymphocytes by human leukocyte interferon: characterization of the augmented activity. Gann 74:887–895

    Google Scholar 

  2. Droller MJ, Lindgren JA, Caessen HE, Perlmann P (1979) Production of prostaglandin E2 by bladder tumor cells in tissue culture and a possible mechanism of lymphocyte inhibition. Cell Immunol 47:261–273

    Google Scholar 

  3. Eremin O, Coombs RRA, Ashby J (1981) Lymphocytes infiltrating human breast cancers lack K-cell activity and show low levels of NK-cell activity. Br J Cancer 44:166–176

    Google Scholar 

  4. Golub SH, Dorey F, Hara D, Morton DL, Burk MW (1982) Systemic administration of human leukocyte interferon to melanoma patients. I Effects on natural killer function and cell populations. JNCI 68:703

    Google Scholar 

  5. Golub SH, D'Amore P, Rainey M (1982) Systemic administration of human leukocyte interferon to melanoma patients. II. Cellular events associated with changes in natural killer cytotoxicity. JNCI 68:711

    Google Scholar 

  6. Grimm EA, Rosenberg SA (1984) In: Pick E (ed) Lymphokindes. Vol 9. Academic Press, Orlando, Florida, p 279

    Google Scholar 

  7. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2 activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823

    Article  CAS  PubMed  Google Scholar 

  8. Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA (1983) Lymphokine activated killer cell phenomenon II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 157:884

    Google Scholar 

  9. Grimm EA, Robb RJ, Roth JA, Neckers LM, Lachman LB, Wilson DJ, Rosenberg SA (1983) Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine activated killer cells. J Exp Med 158:1356

    Article  CAS  PubMed  Google Scholar 

  10. Itoh K, Shiiba K, Yoshinobu S, Suzuki R, Kumagai K (1985) Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon- (IFN-γ). J Immunol 134:3124–3129

    Google Scholar 

  11. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA (1981) Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 41:4420

    Google Scholar 

  12. Merluzzi VJ, Savage DM, Mertelsmann R, Welte K (1984) Generation of nonspecific murine cytotoxic T cells in vitro by purified human interleukin-2. Cell Immunol 84:74

    Google Scholar 

  13. Moore M, Vose BM (1981) Extravascular natural cytotoxicity in man: anti-K562 activity of lymph nodes and tumor infiltrating lymphocytes. Int J Cancer 27:265–272

    Google Scholar 

  14. Moore M, Vose BM (1981) Extravasclar natural cytotoxicity in man: anti-K562 activity of lymph-node and tumor-infiltrating lymphocytes. Int J Cancer 27:265–272

    Google Scholar 

  15. Moy PM, Holmes EC, Golub SH (1985) Depression of natural killer cytotoxic activity in lymphocytes infiltrating human pulmonary tumors. Cancer Res 45:57–60

    Google Scholar 

  16. Moy PM, Holmes EC, Golub SH (1985) A method of improved yield and purity in extracting lymphocytes from lung tumors. J Surg Res 38:17–23

    Google Scholar 

  17. Niitsuma M, Golub SH, Edelstein R, Holmes EC (1981) Lymphoid cells infiltrating human pulmonary tumors effect of intralesional BCG injection. J Natl Cancer Inst 67:997–1003

    Google Scholar 

  18. Perussia B, Starr S, Abraham S, Fanning V, Trinchieri G (1983) Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. J Immunol 130:2133–2141

    Google Scholar 

  19. Pross HF, Baines MG, Rubin P, Shragge P, Patterson MS (1981) Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immun 1:51–63

    Google Scholar 

  20. Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA (1984) Lymphokine-activated killer cells. Lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res 44:1946

    Google Scholar 

  21. Seeley JK, Golub SH (1978) Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities. J Immunol 120:1415–1422

    Google Scholar 

  22. Totterman TH, Hayry P, Saksela E, Timonen T, Eklund B (1978) Cytological and functional analysis of inflammatory infiltrates in human malignant tumors. II. Functional investigations of the infiltrating inflammatory cells. Eur J Immunol 8:872–875

    Google Scholar 

  23. Trinchieri G, Santoli D, Koprowski H (1978) Spontaneous cell-mediated cytotoxicity in humans: Role of interferon and immunoglobulins. J of Immunol 120:1849–1855

    Google Scholar 

  24. Ullberg M, Merill J, Jondal M (1981) Interferon-induced NK augmentation in humans: an analysis of target recognition, effector cell recruitment, and effector cell recycling. Scand J Immunol 14:285–292

    Google Scholar 

  25. Vose BM, Moore M (1979) Suppressor cell activity of lymphocytes infiltrating human lung and breast tumors. Int J Cancer 24:579–585

    Google Scholar 

  26. Vose BM, Vanky F, Argov S, Klein E (1977) Natural cytotoxicity in Man: activity of lymph node and tumor-infiltrating lymphocytes. Eur J Immuno 7:753–757

    Google Scholar 

  27. Yron I, Wood TA, Spiess PJ, Rosenberg SA (1980) In vitro growth of murine T cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. J Immunol 125:238

    Google Scholar 

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Authors and Affiliations

  1. Division of Surgical Oncology, John Wayne Cancer Clinic, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, 90024, Los Angeles, CA, USA

    Timothy M. Anderson, Yukihiro Ibayashi, E. Carmack Holmes & Sidney H. Golub

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  1. Timothy M. Anderson
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  2. Yukihiro Ibayashi
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  3. E. Carmack Holmes
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  4. Sidney H. Golub
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Anderson, T.M., Ibayashi, Y., Holmes, E.C. et al. Modification of natural killer activity of lymphocytes infiltrating human lung cancers. Cancer Immunol Immunother 25, 65–68 (1987). https://doi.org/10.1007/BF00199303

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  • DOI: https://doi.org/10.1007/BF00199303

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